The inherited blindness protein AIPL1 regulates the ubiquitin-like FAT10 pathway.

Mutations in AIPL1 cause the inherited blindness Leber congenital amaurosis (LCA). AIPL1 has previously been shown to interact with NUB1, which facilitates the proteasomal degradation of proteins modified with the ubiquitin-like protein FAT10. Here we report that AIPL1 binds non-covalently to free F...

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Autores principales:	John S Bett, Naheed Kanuga, Emma Richet, Gunter Schmidtke, Marcus Groettrup, Michael E Cheetham, Jacqueline van der Spuy
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1a4f9d7feff04e6d8faa780b2f448247
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spelling	oai:doaj.org-article:1a4f9d7feff04e6d8faa780b2f4482472021-11-18T07:28:46ZThe inherited blindness protein AIPL1 regulates the ubiquitin-like FAT10 pathway.1932-620310.1371/journal.pone.0030866https://doaj.org/article/1a4f9d7feff04e6d8faa780b2f4482472012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22347407/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Mutations in AIPL1 cause the inherited blindness Leber congenital amaurosis (LCA). AIPL1 has previously been shown to interact with NUB1, which facilitates the proteasomal degradation of proteins modified with the ubiquitin-like protein FAT10. Here we report that AIPL1 binds non-covalently to free FAT10 and FAT10ylated proteins and can form a ternary complex with FAT10 and NUB1. In addition, AIPL1 antagonised the NUB1-mediated degradation of the model FAT10 conjugate, FAT10-DHFR, and pathogenic mutations of AIPL1 were defective in inhibiting this degradation. While all AIPL1 mutants tested still bound FAT10-DHFR, there was a close correlation between the ability of the mutants to interact with NUB1 and their ability to prevent NUB1-mediated degradation. Interestingly, AIPL1 also co-immunoprecipitated the E1 activating enzyme for FAT10, UBA6, suggesting AIPL1 may have a role in directly regulating the FAT10 conjugation machinery. These studies are the first to implicate FAT10 in retinal cell biology and LCA pathogenesis, and reveal a new role of AIPL1 in regulating the FAT10 pathway.John S BettNaheed KanugaEmma RichetGunter SchmidtkeMarcus GroettrupMichael E CheethamJacqueline van der SpuyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 2, p e30866 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q John S Bett Naheed Kanuga Emma Richet Gunter Schmidtke Marcus Groettrup Michael E Cheetham Jacqueline van der Spuy The inherited blindness protein AIPL1 regulates the ubiquitin-like FAT10 pathway.
description	Mutations in AIPL1 cause the inherited blindness Leber congenital amaurosis (LCA). AIPL1 has previously been shown to interact with NUB1, which facilitates the proteasomal degradation of proteins modified with the ubiquitin-like protein FAT10. Here we report that AIPL1 binds non-covalently to free FAT10 and FAT10ylated proteins and can form a ternary complex with FAT10 and NUB1. In addition, AIPL1 antagonised the NUB1-mediated degradation of the model FAT10 conjugate, FAT10-DHFR, and pathogenic mutations of AIPL1 were defective in inhibiting this degradation. While all AIPL1 mutants tested still bound FAT10-DHFR, there was a close correlation between the ability of the mutants to interact with NUB1 and their ability to prevent NUB1-mediated degradation. Interestingly, AIPL1 also co-immunoprecipitated the E1 activating enzyme for FAT10, UBA6, suggesting AIPL1 may have a role in directly regulating the FAT10 conjugation machinery. These studies are the first to implicate FAT10 in retinal cell biology and LCA pathogenesis, and reveal a new role of AIPL1 in regulating the FAT10 pathway.
format	article
author	John S Bett Naheed Kanuga Emma Richet Gunter Schmidtke Marcus Groettrup Michael E Cheetham Jacqueline van der Spuy
author_facet	John S Bett Naheed Kanuga Emma Richet Gunter Schmidtke Marcus Groettrup Michael E Cheetham Jacqueline van der Spuy
author_sort	John S Bett
title	The inherited blindness protein AIPL1 regulates the ubiquitin-like FAT10 pathway.
title_short	The inherited blindness protein AIPL1 regulates the ubiquitin-like FAT10 pathway.
title_full	The inherited blindness protein AIPL1 regulates the ubiquitin-like FAT10 pathway.
title_fullStr	The inherited blindness protein AIPL1 regulates the ubiquitin-like FAT10 pathway.
title_full_unstemmed	The inherited blindness protein AIPL1 regulates the ubiquitin-like FAT10 pathway.
title_sort	inherited blindness protein aipl1 regulates the ubiquitin-like fat10 pathway.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/1a4f9d7feff04e6d8faa780b2f448247
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The inherited blindness protein AIPL1 regulates the ubiquitin-like FAT10 pathway.

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